Innate or Adaptive Immunity? The Example of Natural Killer Cells

Vivier, Éric; Raulet, David H.; Moretta, Alessandro; Caligiuri, Michael A.; Zitvogel, Laurence; Lanier, Lewis L.; Yokoyama, Wayne M.; Ugolini, Sophie

doi:10.1126/science.1198687

Cited by 2,298 publications

(2,116 citation statements)

References 78 publications

Supporting

Mentioning

2,065

Contrasting

Unclassified

Order By: Relevance

“…Blocking 4-1BB/4-1BBL interaction in co-cultures of CLL cells with human NK cells, like in AML, significantly increased direct and Rituximab-induced NK granule mobilization, cytotoxicity, target cell lysis and IFN-g production. The variation within the reactivity of NK cells of different donors and the influence of 4-1BBL highlight the fact that NK reactivity is influenced by multiple activating and inhibitory signals [10]. Shifting this balance towards activation by preventing immunoinhibitory 4-1BB/4-1BBL interaction may thus serve well to reinforce direct and Rituximab-induced NK reactivity in CLL.…”

Section: Discussionmentioning

confidence: 99%

“…demonstrated to be compromised in chronic lymphocytic leukemia (CLL) patients, and the FcgR polymorphisms that positively influence Rituximab responses in lymphoma do not predict treatment response in CLL [9]. Both direct anti-tumor reactivity and ADCC of NK cells are influenced by signals of multiple different activating and inhibitory receptors which interact with ligands expressed on tumor cells [10]. Modulating this balance of activating and inhibitory signals is a promising strategy to increase NK-cell reactivity and may also serve to reinforce the therapeutic efficacy of Rituximab in CLL [11].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

4‐1BB ligand modulates direct and Rituximab‐induced NK‐cell reactivity in chronic lymphocytic leukemia

et al. 2011

View full text Add to dashboard Cite

NK cells play an important role in tumor immunosurveillance and largely contribute to the therapeutic success of anti-tumor antibodies like Rituximab. Here, we studied the role of the TNF family member 4-1BB ligand (4-1BBL) during the interaction of NK cells with chronic lymphocytic leukemia (CLL) cells. 4-1BBL was highly expressed on patient B-CLL cells in all 56 investigated cases. Signaling via 4-1BBL following interaction with 4-1BB, which was detected on NK cells of CLL patients but not healthy individuals, led to the release of immunoregulatory cytokines including TNF by CLL cells. CLL patient sera contained elevated levels of TNF and induced 4-1BB upregulation on NK cells, which in turn impaired direct and Rituximab-induced NK-cell reactivity against 4-1BBL-expressing targets. NK-cell reactivity was not only enhanced by blocking the interaction of NK cell-expressed 4-1BB with 4-1BBL expressed by CLL cells, but also by preventing 4-1BB upregulation on NK cells via neutralization of TNF in patient serum with Infliximab. Our data indicate that 4-1BBL mediates NK-cell immunosubversion in CLL, and thus might contribute to the reportedly compromised efficacy of Rituximab to induce NK-cell reactivity in the disease, and that TNF neutralization may serve to enhance the efficacy of Rituximab treatment in CLL.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

4‐1BB ligand modulates direct and Rituximab‐induced NK‐cell reactivity in chronic lymphocytic leukemia

et al. 2011

View full text Add to dashboard Cite

show abstract

“…1-9 In order to fulfill this variety of functions, NK cells use an array of receptors which sense microenvironmental stimuli and mediate appropriate responses. 3,10,11 Several NK receptors are capable of regulating different NK cell functions. For example, the Natural Cytotoxicity Receptors (NCRs) NKp46, NKp30, and NKp44, play an important role in human NK cell-mediated recognition and killing of virally infected and tumor cells, and also induce the release of a number of cytokines and chemotactic factors.…”

Section: Introductionmentioning

confidence: 99%

Nidogen-1 is a novel extracellular ligand for the NKp44 activating receptor

et al. 2018

Self Cite

View full text Add to dashboard Cite

The release of soluble ligands of activating Natural Killer (NK) cell receptors may represent a regulatory mechanism of NK cell function both in physiologic and in pathologic conditions. Here, we identified the extracellular matrix protein Nidogen-1 (NID1) as a ligand of NKp44, an important activating receptor expressed by activated NK cells. When released as soluble molecule, NID1 regulates NK cell function by modulating NKp44-induced IFN-γ production or cytotoxicity. In particular, it also modulates IFN-γ production induced by Platelet-Derived Growth Factor (PDGF)-DD following NKp44 engagement. We also show that NID1 may be present at the cell surface. In this form or when bound to a solid support (bNID1), NID1 fails to induce NK cell cytotoxicity or cytokine release. However, analysis by mass spectrometry revealed that exposure to bNID1 can induce in human NK cells relevant changes in the proteomic profiles suggesting an effect on different biological processes.

show abstract

“…An extra level of regulation of NK cell activation is provided by diverse cytokines (3,4) and the recognition of pathogen-associated molecular patterns through TLRs (5). NK cell activation results not only in a cytotoxic response toward target cells, but also in the secretion of IFN-g and other cytokines and chemokines (6)(7)(8), rendering NK cells capable of modulating the activity of other cells of the immune system and the outcome of the immune response (9)(10)(11).…”

mentioning

confidence: 99%

NK Cells Restrain Spontaneous Antitumor CD8+ T Cell Priming through PD-1/PD-L1 Interactions with Dendritic Cells

Iraolagoitia

Spallanzani

Torres

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

Despite the classical function of NK cells in the elimination of tumor and of virus-infected cells, evidence for a regulatory role for NK cells has been emerging in different models of autoimmunity, transplantation, and viral infections. However, this role has not been fully explored in the context of a growing tumor. In this article, we show that NK cells can limit spontaneous cross-priming of tumor Ag-specific CD8+ T cells, leading to reduced memory responses. After challenge with MC57 cells transduced to express the model Ag SIY (MC57.SIY), NK cell–depleted mice exhibited a significantly higher frequency of SIY-specific CD8+ T cells, with enhanced IFN-γ production and cytotoxic capability. Depletion of NK cells resulted in a CD8+ T cell population skewed toward an effector memory T phenotype that was associated with enhanced recall responses and delayed tumor growth after a secondary tumor challenge with B16.SIY cells. Dendritic cells (DCs) from NK cell–depleted tumor-bearing mice exhibited a more mature phenotype. Interestingly, tumor-infiltrating and tumor-draining lymph node NK cells displayed an upregulated expression of the inhibitory molecule programmed death ligand 1 that, through interaction with programmed death-1 expressed on DCs, limited DC activation, explaining their reduced ability to induce tumor-specific CD8+ T cell priming. Our results suggest that NK cells can, in certain contexts, have an inhibitory effect on antitumor immunity, a finding with implications for immunotherapy in the clinic.

show abstract

Innate or Adaptive Immunity? The Example of Natural Killer Cells

Cited by 2,298 publications

References 78 publications

4‐1BB ligand modulates direct and Rituximab‐induced NK‐cell reactivity in chronic lymphocytic leukemia

4‐1BB ligand modulates direct and Rituximab‐induced NK‐cell reactivity in chronic lymphocytic leukemia

Nidogen-1 is a novel extracellular ligand for the NKp44 activating receptor

NK Cells Restrain Spontaneous Antitumor CD8+ T Cell Priming through PD-1/PD-L1 Interactions with Dendritic Cells

Contact Info

Product

Resources

About